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1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections

BACKGROUND: Infections caused by the multi-drug-resistant Mycobacterium abscessus complex (MabsC) are challenging to treat and often require multiple antimicrobials for a prolonged treatment course and still have poor outcomes. Clofazimine, an oral anti-leprosy drug, has demonstrated good in vitro s...

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Autores principales: Yong, Joy, Lip Chew, Ka, Tambyah, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6809229/
http://dx.doi.org/10.1093/ofid/ofz360.1214
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author Yong, Joy
Lip Chew, Ka
Tambyah, Paul
author_facet Yong, Joy
Lip Chew, Ka
Tambyah, Paul
author_sort Yong, Joy
collection PubMed
description BACKGROUND: Infections caused by the multi-drug-resistant Mycobacterium abscessus complex (MabsC) are challenging to treat and often require multiple antimicrobials for a prolonged treatment course and still have poor outcomes. Clofazimine, an oral anti-leprosy drug, has demonstrated good in vitro susceptibility and is being increasingly employed in treatment regimens for MabsC infections. We performed a drug-use-evaluation of clofazimine in the treatment of MabsC infections. METHODS: A retrospective review was performed for all patients with MabsC infections treated with clofazimine-containing regimens from January 2014 to June 2017. RESULTS: Twenty-nine patients were included. Twelve patients had pulmonary MabsC infections and seventeen had extrapulmonary infections. All isolates had clofazimine minimum-inhibitory-concentration of ≤0.5 mg/L as tested by broth microdilution. Clofazimine was prescribed at initiation of therapy in 31.0% (9/29), as a companion drug during maintenance therapy after initial intravenous therapy in 44.8% (13/29) and as part of salvage therapy due to disease progression or drug intolerance in 24.1% (7/29) of patients. Dosing of clofazimine for the pediatric patients was prescribed at 1–2 mg/kg/day while the adult patients received a range of 50–200 mg/day. Clofazimine was given for a median duration of 148.5 days (range: 14–1212) and most commonly in combination with clarithromycin (82.8%), amikacin (58.6%), and cefoxitin (24.1%). Twelve patients had documented adverse reactions attributable to clofazimine: skin hyperpigmentation (66.7%), abnormal liver function tests (16.7%), and gastrointestinal disturbance (16.7%). Table 1 describes the patients who had clofazimine ceased due to an adverse effect. Nine patients with pulmonary MabsC infections and 16 with extrapulmonary MabsC infections had documented improvement in symptoms. CONCLUSION: Clofazimine as a companion drug in the treatment of MabsC infections was reasonably tolerated over a prolonged period of time. Its availability as an oral active agent makes it an attractive alternative to IV companion drugs and potentially improves compliance to the protracted treatment courses for patients with MabsC infections. [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68092292019-10-28 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections Yong, Joy Lip Chew, Ka Tambyah, Paul Open Forum Infect Dis Abstracts BACKGROUND: Infections caused by the multi-drug-resistant Mycobacterium abscessus complex (MabsC) are challenging to treat and often require multiple antimicrobials for a prolonged treatment course and still have poor outcomes. Clofazimine, an oral anti-leprosy drug, has demonstrated good in vitro susceptibility and is being increasingly employed in treatment regimens for MabsC infections. We performed a drug-use-evaluation of clofazimine in the treatment of MabsC infections. METHODS: A retrospective review was performed for all patients with MabsC infections treated with clofazimine-containing regimens from January 2014 to June 2017. RESULTS: Twenty-nine patients were included. Twelve patients had pulmonary MabsC infections and seventeen had extrapulmonary infections. All isolates had clofazimine minimum-inhibitory-concentration of ≤0.5 mg/L as tested by broth microdilution. Clofazimine was prescribed at initiation of therapy in 31.0% (9/29), as a companion drug during maintenance therapy after initial intravenous therapy in 44.8% (13/29) and as part of salvage therapy due to disease progression or drug intolerance in 24.1% (7/29) of patients. Dosing of clofazimine for the pediatric patients was prescribed at 1–2 mg/kg/day while the adult patients received a range of 50–200 mg/day. Clofazimine was given for a median duration of 148.5 days (range: 14–1212) and most commonly in combination with clarithromycin (82.8%), amikacin (58.6%), and cefoxitin (24.1%). Twelve patients had documented adverse reactions attributable to clofazimine: skin hyperpigmentation (66.7%), abnormal liver function tests (16.7%), and gastrointestinal disturbance (16.7%). Table 1 describes the patients who had clofazimine ceased due to an adverse effect. Nine patients with pulmonary MabsC infections and 16 with extrapulmonary MabsC infections had documented improvement in symptoms. CONCLUSION: Clofazimine as a companion drug in the treatment of MabsC infections was reasonably tolerated over a prolonged period of time. Its availability as an oral active agent makes it an attractive alternative to IV companion drugs and potentially improves compliance to the protracted treatment courses for patients with MabsC infections. [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6809229/ http://dx.doi.org/10.1093/ofid/ofz360.1214 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Yong, Joy
Lip Chew, Ka
Tambyah, Paul
1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections
title 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections
title_full 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections
title_fullStr 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections
title_full_unstemmed 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections
title_short 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections
title_sort 1350. clofazimine as an oral companion drug for treatment of mycobacterium abscessus complex infections
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6809229/
http://dx.doi.org/10.1093/ofid/ofz360.1214
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